1. Field of the Invention
The invention relates to contact lenses and more particularly to methods and compositions for disinfecting such lenses.
2. Brief Description of Related Art
Anti-microbials used in disinfecting ocular prostheses such as contact lenses or employed to preserve ophthalmic formulations designed to be applied directly to the eye or to objects which are in direct contact with the eyes, must be non-irritating and free of any detrimental side effects. Moreover, they must be sufficiently effective against bacteria, viruses and fungi to ensure the sterility of the prostheses or guarantee a reasonable shelf-life of the ophthalmic formulations and thereby prevent infections. The inherent conflict between antimicrobial efficiency on the one hand, and non-irritancy on the other has lead to compromises. The known anti-microbial agents which are found in ophthalmic formulations include:
Benzalkonium chloride, benzethonium chloride, benzyl alcohol, chlorobutanol, chlorhexidine digluconate or diacetate, methyl and propyl hydroxybenzoate(parabens), phenylethyl alcohol, phenylmercuric acetate or nitrate, sorbic acid, thimerosal, alpha-4[1-tris(2-hydroxyethyl) ammonium chloride-2-dibutenyl]poly(1-dimethyl ammonium chloride-2-dibutenyl]-.omega.-tris (2-hydroxyethyl) ammonium chloride, and poly[aminopropyl bis(biguanide)]or poly[hexamethylene-bis(biguanide].
Some attributes of a disinfectant/preservative, which would be very desirable from an ophthalmic point of view, are:
1) Bactericidal and fungicidal activity at concentration levels which are much lower than those likely to cause damage to mammalian cells, i.e. selective toxicity. PA0 2) Nonirritant to the ocular surface upon topical application. PA0 3) Innocuous toward corneal epithelial or endothelial cells. PA0 4) Effective in the physiological Ph range, i.e. Ph 6-8. PA0 5) Not acting as a sensitizing agent to ocular tissues (unlike thimerosal and chlorhexidine). PA0 6) Readily compatible in aqueous solution. PA0 7) Chemically and thermally stable in aqueous media and able to withstand radiation sterilization. PA0 8) Possessing prolonged chemical stability in aqueous mixtures at physiological pH's (acceptable shelf-life). PA0 9) Not absorbed into the polymer matrix of hydrogel lenses thereby not accumulating within the matrix of the lens nor leaching into the ocular tissues upon application of the lens to the eye. PA0 10) Not adsorbed adversely onto the surface of the contact lenses, so as to diminish the water wettability of such lenses, nor increases the water/lens interfacial tension appreciably and thereby reduce lens ocular compatibility and perceived in-eye comfort. PA0 11) Not interfering with the solubility or other properties of the components of the ocular formulation to be preserved such as contact lens wetting, film forming, and viscosity-modifying agents or therapeutic agents. PA0 12) Neither absorbed into nor adsorbed onto the polymers used in the construction of eye-dropper containers (bottles). PA0 13) Not absorbed systemically, i.e. by the bodily organs via the circulatory system. PA0 14) Free of toxic heavy metal ions which may act as cumulative poisons in the body.
It is important to note here that none of the earlier listed presently known preservatives fulfill all of the above criteria especially those listed as items 9 and 10.
Until recently, virtually all of the commercially available hydrogel lenses were fabricated from neutral polymeric materials such as poly(HEMA). However, the introduction of disposable lenses, such as those sold under the brand name "Acuvue" by Johnson and Johnson, Inc., has led to the reintroduction and widespread use of a contact lens material fabricated by the anionic Etafilcon A.RTM. and containing methylmethacrylic acid groups. Such lenses are not ideally suited for use with ophthalmic solutions containing polyquaternary ammonium antimicrobial agents, since the latter agents react electrostatically with the surfaces of such materials.
Clinical impressions suggest that such polyquaternary ammonium disinfectant solutions do indeed adsorb to the surfaces of certain soft lens materials, especially anionic materials, and cause ocular discomfort. It is essential for the lens to retain its wettability and low interfacial tension against tear, and allow a continuous film of tear fluid covering, in order to remain acceptable to the contact lens wearer.
While there may be many industrial and even pharmaceutical disinfectants and preservatives available, their suitability to ophthalmic applications is never obvious and their potential must be first recognized, then carefully formulated and clinically tested to achieve a satisfactory balance of efficacy, safety and contact lens compatibility.
The present invention provides a means of disinfecting a contact lens with an agent which satisfies the 12 attributes listed above as desirable for the anti-microbial agent.